Showing posts with label amino acids. Show all posts
Showing posts with label amino acids. Show all posts
9.5.12
Do L-tyrosine supplements improve Crohn's symptoms?
Tyrosine from University of Maryland Medical Center
"Amino Acid Responsive Crohn’s Disease: a case study" in Clin Exp Gasteroenterol (2010)
"... the patient was then taking the following in divided daily doses: 300 mg 5-HTP, 6000 mg L-tyrosine, 240 mg L-dopa, and 4500 mg L-cysteine with cofactors. Following this change in amino acid dosing values, the patient continued to be asymptomatic, a state that exists to this day as long as he is compliant with the prescribed amino acid dosing values."
Does 5-HTP supplementation improve Crohn's symptoms?
5-HTP from The University of Maryland Medical Center
"The serotonin precursor 5-hydroxytryptophan reinforces intestinal barrier function" from Top Institute Food and Nutrition, Wageningen [no date]
"Tight junctions between intestinal epithelial cells form a selective barrier that contributes to gut homeostasis. Alterations in intestinal barrier function are considered to be early factors in the pathogenesis of irritable bowel syndrome (IBS). ... Oral administration of 5-HTP reinforces small intestinal barrier function by lowering intestinal sugar permeability, inducing the expression of the tight junction protein ZO-1 and rearranging tight junction proteins. These changes are associated with 5-HTP-induced alterations in mucosal serotonin metabolism. These data point to a role for serotonergic metabolism in reinforcing intestinal barrier function."
"Physiological roles of 5-HTP in the brain have not been reported. On the other hand, 5-HTP has a specific function in the gut. As a unique BH4 [ 6R-L-erythro-5,6,7,8-tetrahydrobiopterin] transport mechanism, BH4 that transiently enters cells can be rapidly oxidized to BH2 and is exported back to the extracellular space. Meanwhile, the intestinal epithelial cells take up BH4 as its reduced form. Therefore, the intestine shares a unique BH4 transporter mechanism and a specific function of 5-HTP. Further studies would clarify the intestine-specific machinery linking the specific mechanism of BH4-dependent 5-HTP production to the specific function of 5-HTP. A 5-HT precursor 5-HTP is sometimes administered to patients with metabolic disorder.27 The finding on the function of 5-HTP in the intestine might create an opportunity to explore the effects of exogenously-applied 5-HTP on the intestine in man."
"Gut hormones: emerging role in immune activation and inflammation" in Clinical and Experimental Immunology (2010) [full article]
"The studies discussed in this review provide evidence in favour of a key role of gut hormones in intestinal inflammation. In addition to the contribution in GI physiology, such as motility and secretion, gut hormones can also play an important role in immune activation and in the generation of inflammation in gut. The precise mechanisms by which gut hormones regulate the inflammation remain to be determined. The data generated from the studies on 5-HT in gut inflammation suggest strongly that increased 5-HT released by luminal inflammatory stimuli can activate immune cells such as macrophages, dendritic cells, lymphocytes and enteric nerves via specific 5-HT receptors, which can enhance the production of proinflammatory mediators via triggering activation of the NF-κB pathway and/or other possible proinflammatory signalling systems, and which subsequently can up-regulate the inflammatory response (Fig. 1). It will be interesting to see roles of specific 5-HT receptor subtype(s) in immune activation and generation of intestinal inflammation.
...
These studies provide novel information on the role of gut hormones in immune signalling and regulation of gut inflammation. Despite being a challenging and complicated area to explore, recent studies on immunoendocrine interaction has generated new interest to elucidate the role of gut hormones in the inflammatory process and immune function. In addition to enhancing our understanding on the pathogenesis of inflammatory changes, these studies give new information on 5-HT and Cgs [chromogranins] in the context of immunoendocrine interactions in gut and intestinal homeostasis. This is very important, due not only to the alteration in enteric endocrine cells functions observed in various GI inflammatory conditions but also in non-GI inflammatory disorders and functional GI disorders such as IBS. These data may have implications in understanding the role of gut hormone in the pathogenesis of both GI and non-GI inflammation, which may lead ultimately to improved therapeutic strategies in inflammatory disorders."
See my post entitled Does serotonin production worsen Crohn's symptoms?"
4.5.12
Does L-carnitine improve Crohn's symptoms?
"L-carnitine and intestinal inflammation" in Vitamins and the immune system (2011) (pp. 353-366)
"The intestinal barrier is one of the most dynamic surfaces of the body. It is here where a single layer of epithelial cells mediates the intricate encounters that occur between the host's immune system and a multitude of potential threats present in the intestinal lumen. Several key factors play an important role in the final outcome of this interaction, including the state of oxidative stress, the level of activation of the immune cells, and the integrity of the epithelial barrier. This chapter describes the main evidence demonstrating the impact that L-carnitine has on each of these factors. These findings, combined with the demonstrated safety profile of L-carnitine, underscore the potential therapeutic value of L-carnitine supplementation in humans suffering from intestinal inflammation and highlight the functional data supporting an association between Crohn's disease and mutations in the L-carnitine transporter genes."
L-carnitine to Treat Fatigue Associated With Crohn's Disease, University of California, San Francisco
ClinicalTrials.gov identifier: NCT01523106
Estimated Enrollment: 200
Study Start Date: February 2012
Estimated Study Completion Date: February 2013
Active comparator: Patients will take 4 grams of L-carnitine (2 grams twice daily) for 3 months
"Role of carnitine in disease" in Nutrition and Metabolism (2010)
"Carnitine transporter mutations in Crohn's disease consists of missense mutation(s) in the gene coding plasma membrane transporter OCTN1 (SLC22A4) and/or mutation(s) in the promoter of the gene encoding OCTN2 (SLC22A5) [14,35]. Manifestation of these mutations results in disruption of a heat shock binding element decreasing the transport function (OCTN1), and reduced expression (through OCTN2 mutation) which both result in carnitine deficiency [14]. These mutations are in strong linkage disequilibrium, creating a two-allele risk haplotype and hence increasing the overall risk of this disease [14]."
"Identifying new therapeutic targets for treatment of Crohn's disease: The role of CD47 and L-carnitine in the pathogenesis and treatment of a murine model of intestinal inflammation", Geneviève Fortin
McGill University (2010)
"L-carnitine is an amino acid derivative normally present in meat and dairy products and is also available as an over-the-counter nutritional supplement. Since mutations in the L-carnitine transporters, OCTN1 and OCTN2, were found to be associated with CD, we sought to examine its role in the development of intestinal inflammation. Remarkably, L-carnitine displayed immunosuppressive properties both in vitro and in vivo, effectively suppressing both the innate and the adaptive arms of the immune response and resulting in a significant reduction in the development of intestinal inflammation."
"We have thus identified CD47 as an important regulator of SIRPα+ DC trafficking, and demonstrate that this DC subset is implicated in the development of intestinal inflammation. Additionally, we have identified two promising new therapeutic candidates, CD47-fc and L-carnitine, for the treatment of CD."
Estimated Enrollment: 200
Study Start Date: February 2012
Estimated Study Completion Date: February 2013
Active comparator: Patients will take 4 grams of L-carnitine (2 grams twice daily) for 3 months
"Role of carnitine in disease" in Nutrition and Metabolism (2010)
"Carnitine transporter mutations in Crohn's disease consists of missense mutation(s) in the gene coding plasma membrane transporter OCTN1 (SLC22A4) and/or mutation(s) in the promoter of the gene encoding OCTN2 (SLC22A5) [14,35]. Manifestation of these mutations results in disruption of a heat shock binding element decreasing the transport function (OCTN1), and reduced expression (through OCTN2 mutation) which both result in carnitine deficiency [14]. These mutations are in strong linkage disequilibrium, creating a two-allele risk haplotype and hence increasing the overall risk of this disease [14]."
"Identifying new therapeutic targets for treatment of Crohn's disease: The role of CD47 and L-carnitine in the pathogenesis and treatment of a murine model of intestinal inflammation", Geneviève Fortin
McGill University (2010)
"L-carnitine is an amino acid derivative normally present in meat and dairy products and is also available as an over-the-counter nutritional supplement. Since mutations in the L-carnitine transporters, OCTN1 and OCTN2, were found to be associated with CD, we sought to examine its role in the development of intestinal inflammation. Remarkably, L-carnitine displayed immunosuppressive properties both in vitro and in vivo, effectively suppressing both the innate and the adaptive arms of the immune response and resulting in a significant reduction in the development of intestinal inflammation."
"We have thus identified CD47 as an important regulator of SIRPα+ DC trafficking, and demonstrate that this DC subset is implicated in the development of intestinal inflammation. Additionally, we have identified two promising new therapeutic candidates, CD47-fc and L-carnitine, for the treatment of CD."
30.4.12
Are arginine and glutamate a dynamic duo?
See my post entitled "Do L-arginine supplements reduce Crohn's symptoms?" for specific benefits of L-arginine supplementation
See my post entitled "Do L-glutamine supplements reduce Crohn's symptoms?" for specific benefits of L-gluatmine supplementation.
"Uncoupling gene–diet interactions in inflammatory bowel disease (IBD)" in Genes Nutr (2007)
"The amino acids arginine and glutamine are considered non-essential amino acids, but may be depleted during an immune response. Arginine is the sole substrate for nitric oxide synthase, necessary for the synthesis of nitric oxide that is secreted by macrophages to kill pathogens. Glutamine is a specific fuel for the proliferation of lymphocytes. Many sulphur amino acids act as substrates for acute phase protein and immunoglobulin synthesis, and the intake of these molecules is particularly important for glutathione production. An insufficient intake of sulphur amino acids will both exert a pro-inflammatory influence, and reduce the efficiency of the specific immune response."
"Combined Glutamine and Arginine Decrease Proinflammatory Cytokine Production by Biopsies from Crohn's Patients in Association with Changes in Nuclear Factor-κB and p38 Mitogen-Activated Protein Kinase Pathways" in American Society for Nutrition (2008)
" Arghigh/Glnhighdecreased the production of TNFα, IL-1β, IL-8, and IL-6 (each P < 0.01). ... Combined pharmacological doses of Arg and Gln decreased TNFα and the main proinflammatory cytokines release in active colonic CD biopsies via NF-κB and p38 MAPK pathways. These results could be the basis of prospective studies evaluating the effects of enteral supply of combined Arg and Gln during active CD."
"Combined infusion of glutamine and arginine: does it make sense?" in Current Opinion in Clinical Nutrition & Metabolic Care (2010)
"Recent findings: In addition to its role as a fuel, glutamine regulates gut barrier function, immuno-inflammatory response and antioxidant status. Arginine metabolism leads to nitric oxide and/or polyamines and thus modulates the immuno-inflammatory response and wound healing. Glutamine and arginine metabolism are closely related, and therefore may give additive or antagonist effects on several pathways. The effects of combined arginine and glutamine are still poorly documented. Combined administration of arginine and glutamine resulted in additive or synergistic effects on gut barrier function and inflammatory response but arginine reduced glutamine protection against oxidative stress. Preliminary data indicate that the combination may be beneficial during intestinal inflammation, whereas data in surgical or critically ill patients are still lacking.
Summary: Mostly speculative effects of combined infusion of arginine and glutamine are discussed. Future studies are needed in specific pathophysiological conditions to assess whether this combination is beneficial or detrimental."
"Potential for amino acid supplementation during Inflammatory Bowel Diseases" in Inflammatory Bowel Diseases (2010)
"Experimental data evaluating pharmaconutrition with amino acids such as glutamine and arginine in colitis models are promising but further studies are required to evaluate the clinical effects of these amino acids. While modern therapies have improved efficacy, they are expensive and have some side effects. In contrast, amino acid supplementation would have a lower cost, but current clinical data do not support the use of amino acid supplementation in IBD. Future directions of research should be 1) to evaluate the combination of amino acids and to understand how they work; 2) to develop drug delivery and targeting issues to achieve adequate concentrations at the site of inflammation; 3) to study dose response and toxicity; and 4) to address the concept of combined treatment associating nutrient and drug."
"Glutamine and Whey Protein Improve Intestinal Permeability and Morphology in Patients with Crohn's Disease: A Randomized Controlled Trial" in Digestive Diseases and Sciences (2012)
"Intestinal permeability and morphology improved significantly in both glutamine and ACG."
Do L-arginine supplements reduce Crohn's symptoms?
Aginine from Wikipeda
L-arginine from MedlinePlus
In a grain-free diet nuts are the best source.
"Increased serum levels of L-arginine in ulcerative colitis and correlation with disease severity" in Inflamm Bowel Dis (2010)
"Serum L-Arg levels correlate with UC disease severity but availability is not increased due to competitive inhibition by L-Orn and L-Lys. Our findings suggest that L-Arg uptake by cells in the inflamed colon is defective, which may contribute to the pathogenesis of UC. Studies delineating the mechanism of uptake inhibition could enhance our understanding of UC or lead to novel treatment options."
"L-arginine Supplementation Improves Responses to Injury and Inflammation in Dextran Sulfate Sodium Colitis" in PLoS ONE (2012)
L-arginine from MedlinePlus
In a grain-free diet nuts are the best source.
"Increased serum levels of L-arginine in ulcerative colitis and correlation with disease severity" in Inflamm Bowel Dis (2010)
"Serum L-Arg levels correlate with UC disease severity but availability is not increased due to competitive inhibition by L-Orn and L-Lys. Our findings suggest that L-Arg uptake by cells in the inflamed colon is defective, which may contribute to the pathogenesis of UC. Studies delineating the mechanism of uptake inhibition could enhance our understanding of UC or lead to novel treatment options."
"L-arginine Supplementation Improves Responses to Injury and Inflammation in Dextran Sulfate Sodium Colitis" in PLoS ONE (2012)
"Luminex-based multi-analyte profiling demonstrated that there was a marked reduction in proinflammatory cytokine and chemokine expression with L-Arg treatment. Genomic analysis by microarray demonstrated that DSS-treated mice supplemented with L-Arg clustered more closely with mice not exposed to DSS than to those receiving DSS alone, and revealed that multiple genes that were upregulated or downregulated with DSS alone exhibited normalization of expression with L-Arg supplementation. Additionally, L-Arg treatment of mice with DSS colitis resulted in increased ex vivomigration of colonic epithelial cells, suggestive of increased capacity for wound repair. ... These preclinical studies indicate that L-Arg supplementation could be a potential therapy for IBD, and that one mechanism of action may be functional enhancement of iNOS activity."
5.7.11
Do L-glutamine supplements reduce Crohn's symptoms?
Glutamine from Wikipedia
"The most eager consumers of glutamine are the cells of intestines...."
Glutamine from The University of Maryland Medical Center
"Glutamine is the most abundant amino acid (building block of protein) in the body. The body can make enough glutamine for its regular needs, but extreme stress (the kind you would experience after very heavy exercise or an injury), your body may need more glutamine than it can make. Most glutamine is stored in muscles followed by the lungs, where much of the glutamine is made.
"The most eager consumers of glutamine are the cells of intestines...."
Glutamine from The University of Maryland Medical Center
"Glutamine is the most abundant amino acid (building block of protein) in the body. The body can make enough glutamine for its regular needs, but extreme stress (the kind you would experience after very heavy exercise or an injury), your body may need more glutamine than it can make. Most glutamine is stored in muscles followed by the lungs, where much of the glutamine is made.
...
Glutamine helps to protect the lining of the gastrointestinal tract known as the mucosa. For that reason, some have suggested that people who have inflammatory bowel disease (ulcerative colitis and Crohn' s disease) may not have enough glutamine. However, 2 clinical trials found that taking glutamine supplements did not improve symptoms of Crohn' s disease. More research is needed."
"Dietary Factors in the Modulation of IBD: Glutamine" from Medscape Today
"Glutamine is sometimes advocated as being beneficial in the management of inflammation. Although not an essential amino acid, glutamine is believed to play a role in the maintenance of the colonic mucosal barrier, and is an energy substrate for colonic cells. ...
However, not all of the studies regarding glutamine show positive benefit in IBD. When administered in a trinitrobenzenesulfonic acid-induced colitis model, there was actually a worsening of intestinal inflammation. Other studies in different models, however, have shown an improvement. As suggested by Akobeng and colleagues, there may be an optimal level of glutamine necessary for improvement; alteration from that level may have deleterious effects."
"Glutamine Prevents Fibrosis Development in Rats with Colitis Induced by 2,4,6-Trinitrobenzene Sulfonic Acid" in The Journal of Nutrition (2010)
"Our findings suggest that glutamine treatment not only attenuates the outcome of TNBS-induced colitis by reducing the inflammatory response but also by downregulating the increased expression of several gene pathways that contribute to the accumulation of matrix proteins. This molecule may be an interesting candidate for reducing the risk of fibrosis and stricture formation in inflammatory bowel disease."
"Glutamine and Whey Protein Improve Intestinal Permeability and Morphology in Patients with Crohn’s Disease: A Randomized Controlled Trial" In Digestive Diseases and Sciences (2012)
"Glutamine, the major fuel for the enterocytes, may improve IP. ... [A] glutamine group (GG) or active control group (ACG) and were given oral glutamine or whey protein, respectively.... Intestinal permeability and morphology improved significantly in both glutamine and ACG."
Glutamine helps to protect the lining of the gastrointestinal tract known as the mucosa. For that reason, some have suggested that people who have inflammatory bowel disease (ulcerative colitis and Crohn' s disease) may not have enough glutamine. However, 2 clinical trials found that taking glutamine supplements did not improve symptoms of Crohn' s disease. More research is needed."
"Dietary Factors in the Modulation of IBD: Glutamine" from Medscape Today
"Glutamine is sometimes advocated as being beneficial in the management of inflammation. Although not an essential amino acid, glutamine is believed to play a role in the maintenance of the colonic mucosal barrier, and is an energy substrate for colonic cells. ...
However, not all of the studies regarding glutamine show positive benefit in IBD. When administered in a trinitrobenzenesulfonic acid-induced colitis model, there was actually a worsening of intestinal inflammation. Other studies in different models, however, have shown an improvement. As suggested by Akobeng and colleagues, there may be an optimal level of glutamine necessary for improvement; alteration from that level may have deleterious effects."
"Glutamine Prevents Fibrosis Development in Rats with Colitis Induced by 2,4,6-Trinitrobenzene Sulfonic Acid" in The Journal of Nutrition (2010)
"Our findings suggest that glutamine treatment not only attenuates the outcome of TNBS-induced colitis by reducing the inflammatory response but also by downregulating the increased expression of several gene pathways that contribute to the accumulation of matrix proteins. This molecule may be an interesting candidate for reducing the risk of fibrosis and stricture formation in inflammatory bowel disease."
"Glutamine and Whey Protein Improve Intestinal Permeability and Morphology in Patients with Crohn’s Disease: A Randomized Controlled Trial" In Digestive Diseases and Sciences (2012)
"Glutamine, the major fuel for the enterocytes, may improve IP. ... [A] glutamine group (GG) or active control group (ACG) and were given oral glutamine or whey protein, respectively.... Intestinal permeability and morphology improved significantly in both glutamine and ACG."
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